Abstract:
Background Tripartite motif 15 (TRIM15) is widely involved in many cellular biological processes, such as gene transcriptional regulation, cell proliferation and differentiation, signal transduction and immune response. It is closely associated with the occurrence and development, invasion and metastasis, and drug tolerance of a variety of malignant tumors. However, the role of TRIM15 in pancreatic cancer is unclear.
Objective To investigate the expression of TRIM15 in pancreatic ductal adenocarcinoma (PDAC) tissues and explore the possibility of TRIM15 as a potential biomarker for the diagnosis of pancreatic cancer.
Methods GEO database was used to screen the differential genes related to invasion and metastasis of pancreatic cancer; Immunohistochemical staining was used to detect TRIM15 protein expression levels in 72 PDAC samples, 40 paracancer samples of pancreatic cancer, 5 chronic pancreatitis samples, 5 intraductal papillary mucinous tumors of pancreas, 6 positive and 6 negative lymph nodes that were collected from Qingdao Municipal Hospital from June 2018 to June 2022, then the clinicopathological features were analyzed. Univariate and multivariate Cox were used to analyze the prognostic risk factors of pancreatic cancer; Kaplan-Meier method was used to analyze the effect of TRIM15 expression level on the overall survival time of pancreatic cancer patients. GO analysis and KEGG pathway enrichment analysis were both used to analyze the signal pathways and main functions of TRIM15.
Results Four differentially expressed genes KLK8, TRIM15, CCL2 and FOSB related to pancreatic cancer invasion and metastasis were identified by GEO database; Immunohistochemical staining indicated that the expression level of TRIM15 in PDAC was significantly higher than those in paracancerous tissues (P<0.05), chronic pancreatitis tissues and pancreatic intraductal papillary mucinous tumors of the pancreas (P<0.05). The high expression of TRIM15 in PDAC was correlated with tumor stage, tumor diameter, lymph node metastasis, and distant organ metastasis (all P<0.05). Cox regression analysis showed that distant metastasis and TRIM15 expression level (P <0.05) were independent factors affecting the prognosis of PDAC. Kaplan-Meier survival analysis showed that positive expression of TRIM15 was associated with low survival in PDAC patients (P<0.05). Moreover, TRIM15 was involved in extracellular matrix receptor interaction, protein digestion and absorption, local adhesion, as well as PI3K-Akt signaling pathway confirmed by GO analysis and KEGG pathway enrichment analysis.
Conclusion TRIM15 plays an important role in the pathogenesis and development of pancreatic cancer, which may influence the development of the disease through the regulation of PI3K-Akt signaling pathway. Positive expression of TRIM15 is an independent risk factor for poor prognosis in PDAC patients, and clinical detection of TRIM15 expression is helpful to the prognosis of pancreatic cancer patients.
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